P
US6946543B2ExpiredUtilityPatentIndex 88

Truncated EGF receptor

Assignee: LUDWIG INST CANCER RESPriority: Jun 28, 2000Filed: Jun 28, 2001Granted: Sep 20, 2005
Est. expiryJun 28, 2020(expired)· nominal 20-yr term from priority
Inventors:WARD COLIN WESLEYMCKERN NEIL MORETONLOVRECZ GEORGE OSCARJORISSEN ROBERT NICHOLASGARRETT THOMAS PETER JOHNELLEMAN THOMAS CHARLESBURGESS ANTONY WILKESADAMS TIMOTHY EDWARDDOMAGALA TERESA ANNENICE EDOUARD
A61P 35/00A61P 43/00A61P 17/06C07K 14/71
88
PatentIndex Score
34
Cited by
19
References
23
Claims

Abstract

The present invention relates to truncated EGF receptor molecules that exhibit increased binding affinities for EGFR ligands such as EGF and TGF-α. The present invention also relates to methods of screening for EGF receptor ligands and methods of treatment which involve the use of these molecules.

Claims

exact text as granted — not AI-modified
1. An isolated truncated ErbB1 ectodomain comprising at least residues 1-492 of ErbB1 and lacking at least the third to seventh modules of the ErbB1 CR2 domain such that the truncated ErbB1 ectodomain has an increased binding affinity for at least one ErbB1 ligand when compared to the full length ErbB1 ectodomain. 
     
     
       2. The truncated ErbB1 ectodomain as claimed in  claim 1  wherein the truncated ErbB1 ectodomain has an increased binding affinity for EGF and/or TGF-α. 
     
     
       3. The truncated ErbB1 ectodomain as claimed in  claim 2  wherein the truncated ErbB1 ectodomain lacks at least the second to seventh modules of the CR2 domain. 
     
     
       4. The truncated ErbB1 ectodomain as claimed in  claim 2  wherein the truncated ErbB1 ectodomain further lacks a portion of the first module of the CR2 domain. 
     
     
       5. The truncated ErbB1 ectodomain as claimed in  claim 2  wherein the truncated ErbB1 ectodomain lacks residues 514-621. 
     
     
       6. The truncated ErbB1 ectodomain as claimed in  claim 2  wherein the truncated ErbB1 ectodomain lacks residues 502-621. 
     
     
       7. The truncated ErbB1 ectodomain as claimed in  claim 2  wherein the truncated ErbB1 ectodomain has an affinity for EGF such that the Kd is less than 30 nM. 
     
     
       8. The truncated ErbB1 ectodomain as claimed in  claim 2  wherein the truncated ErbB1 ectodomain has an affinity for TGF-α such that the Kd is less than 45 nM. 
     
     
       9. A chimeric or fusion protein comprising a truncated ErbB1 ectodomain as claimed in  claim 2 . 
     
     
       10. The chimeric or fusion protein as claimed in  claim 9  wherein the truncated ErbB1 ectodomain is conjugated to an immunoglobulin constant domain. 
     
     
       11. The truncated ErbB1 ectodomain as claimed in  claim 1  wherein the truncated ErbB1 ectodomain lacks at least the second to seventh modules of the CR2 domain. 
     
     
       12. The truncated ErbB1 ectodomain as claimed in  claim 1  wherein the truncated ErbB1 ectodomain further lacks a portion of the first module of the CR2 domain. 
     
     
       13. The truncated ErbB1 ectodomain as claimed in  claim 1  wherein the truncated ErbB1 ectodomain lacks residues 514-621. 
     
     
       14. The truncated ErbB1 ectodomain as claimed in  claim 1  wherein the truncated ErbB1 ectodomain lacks residues 502-621. 
     
     
       15. The truncated ErbB1 ectodomain as claimed in  claim 1  wherein the truncated ErbB1 ectodomain has an affinity for EGF such that the Kd is less than 30 nM. 
     
     
       16. The truncated ErbB1 ectodomain as claimed in  claim 1  wherein the truncated ErbB1 ectodomain has an affinity for TGF-α such that the Kd is less than 45 nM. 
     
     
       17. A chimeric or fusion protein comprising a truncated ErbB1 ectodomain as claimed in  claim 1 . 
     
     
       18. The chimeric or fusion protein as claimed in  claim 17  wherein the truncated ErbB1 ectodomain is conjugated to an immunoglobulin constant domain. 
     
     
       19. A pharmaceutical composition comprising the chimeric or fusion construct as claimed in  claim 17  and a pharmaceutically acceptable carrier or diluent. 
     
     
       20. A pharmaceutical composition comprising the truncated ErbB1 ectodomain as claimed in  claim 1  and a pharmaceutically acceptable carrier or diluent. 
     
     
       21. An isolated truncated ErbB1 ectodomain comprising residues 1-501 or residues 1-513 of the ErbB1 ectodomain and lacking at least the third to seventh modules of the ErbB1 CR2 domain such that the truncated ErbB1 ectodomain has an increased binding affinity for at least one ErbB1 ligand when compared to the full length ErbB1 ectodomain. 
     
     
       22. An isolated truncated ErbB1 ectodomain consisting of residues 1-501 or 1-513 of the ErbB1 ectodomain. 
     
     
       23. A dimer of the chimeric or fusion protein of  claim 18  or  claim 10 .

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